RDT – Maximising Harm, Australia-wide

rdt2In January 2016, an eminent Australian barrister discussed issues raised when a person driving a motor vehicle is roadside tested and found positive for ingestion of cannabis. The opinion alluded to the extension of this legislation to future Australian medical patients who, having reasonably and lawfully ingested cannabis as part of their pharmacotherapy, will inevitably face the same legal standards as those who have ingested cannabis ‘recreationally’. Furthermore, the opinion claimed the underlying drug1-driving laws are grossly unfair and not based on data or scientific knowledge. This opinion called into question not only the fairness of the laws, but the very evidence supporting the roadside drug testing procedures, based on testing of saliva/oral fluid that underpin present laws.

Fundamental pharmacological principles propose a drug effect will be related in a graded response to dose, up to a maximum effect. After administration the dose eventually brings to equilibrium (not equalises) throughout body fluids and tissues. The degree of dilution in the body is reflected in drug blood concentrations. The pharmacological effects are reflected in the relevant drug (or metabolite) concentrations in the receptor-containing site of action, the ‘biophase’. After equilibration, sampled biofluid concentrations (blood, plasma or serum2) can act as a proxy for those in the biophase and thereby allow greater insight into responses than can be gained from dose alone.

medical-cannabis-flachen

The intrinsic variability in how the body handles a drug becomes magnified by unpredictability in the rate and extent of systemic absorption associated with the mode of administration. This is typically referred to as pharmacokinetic variability (what the body does to a drug in a quantitative sense). The relationship between dose and resultant time-course of biofluid (particularly blood) drug concentrations can be complex and such concentrations are the primary determinants of drug effects. Moreover, the same drug doses, or biofluid drug concentrations, do not necessarily produce the same levels of pharmacological effects. This is referred to as pharmacodynamic variability (what a drug does to the body in a quantitative sense) and is typically reflected by drug concentrations associated with the same effects differing between individuals and even within individuals.

tetrahydrocannabinolCannabis, being a natural plant product, consists of many hundreds of phytochemical substances, some with chemical structures recognisably similar to ∆9-tetrahydrocannabinol (THC). These are collectively referred to as cannabinoids and many are active, pharmacologically. Both the actual and relative amounts of these substances vary with many influences, including strain of the plant, parts harvested and methods of processing. THC is the most studied substance, being recognised as having a variety of salutary pharmacological effects and being the principal neuro-active substance in cannabis. Many other phytocannabinoids, such as the acid precursors of THC (THCa) and Cannabidiol (CBDa), Cannabigerol (CBG) and Cannabidivarin (CBDv) for example, are currently under investigation for possible pharmacotherapeutic uses. Cannabis also contains several hundred non-cannabinoid substances, with many contributing to the therapeutic and other pharmacological effects attributable to cannabis (terpenes, for example). 

rdtMany laboratory research studies of cannabis determine biofluid concentrations of THC after ingestion. These typically show marked variability of the biofluid (blood) THC concentration-time profiles despite apparently the same experimental conditions. Controlled laboratory research studies performed in healthy volunteer subjects who used cannabis for purported recreational purposes found a reasonably consistent ‘impairment relationship’. However, the same conclusions have not been well supported from opportunistic studies performed by the comparison of fatal and non-fatal road traffic crashes where;

“Equating impairment to blood cannabinoid concentrations is not straightforward: a clear dose-response relationship has not been established, unlike for alcohol. The pharmacology of cannabis makes it difficult to interpret cannabinoid concentrations, both in life and in post-mortem blood samples”.

rdt3It is argued the principle of using oral fluid for cannabis (THC) testing is problematic. Oral fluid is not a ‘body fluid pool’  such as blood that contains drug concentrations in equilibrium with those in the biophase. Whereas blood provides a reasonable proxy for the pharmacological effects of cannabis (particularly THC), oral fluid THC concentrations may be associative with, but are not causative of, the pharmacological effects attributed to THC. Oral fluid is useful for supposing the past ingestion of a drug, but has reliability limitations in predicting the acute pharmacological effects of a drug. However, its usefulness was found to be more limited than anticipated, mainly due to unpredictable inter- and intra-individual variability. Saliva sampling was largely abandoned in pharmacotherapy research only to become progressively re-introduced over the past decade by the forensic quest for a convenient, non-invasive sampling matrix to test for ‘drugs of abuse.

drugsinbloodWith some notable exceptions (anti-coagulants for example), drugs rarely act by being in the blood. The blood ‘pool’ acts as a conduit for drug delivery to, and removal from, the tissues, including the biophase. The important point is drugs typically distribute between blood, serum or plasma, blood cells and tissues, in a rational manner so sample-able blood drug concentration measurements may be used as a reasonable proxy for biophase concentrations and thus pharmacological effects. Oral fluid is not a body ‘pool’ with an anatomically defined distribution and the oral fluid concentrations of drugs need bear no rational relationship to the amount of that substance present in the body; moreover, unlike drug blood concentrations, they do not have an intrinsic role in driving the attributed pharmacological effect.

Image result for transpulmonary vaporization of cannabisRoadside testing for cannabis (THC) ought to be capable of providing a useful predictor of diminished performance, rather than evidence of ingestion alone. Although blood concentrations of a drug can be useful proxies for the relevant biophase concentrations, with modes of rapid systemic delivery (transpulmonary, i.e., inhaled into lungs), there is often a marked and highly variable mismatch (hysteresis) between the times-courses of drug effects and the blood concentrations until equilibration occurs. Hysteresis depends on many factors, including how and when blood sampling is performed, as well as the properties of a drug. Hysteresis complicates the interpretation of effects from measured drug biofluid concentrations alone, mainly in the first several hours after drug ingestion. Thereafter, the time course of drug, blood and effect occur essentially in parallel (pseudo-equilibrium). The maximum measured biofluid drug concentration (Cmax) is the most obviously affected metric, often occurring at a time well different to the maximum drug effect (Emax). Various pharmacokinetic-pharmacodynamic models have been proposed to account for this observation and some have been proposed for THC, but it seems none have been developed specifically for THC and driving impairment.

drugsaustralia

All Australian states and territories have instituted roadside (and certain workplace) oral fluid testing for methamphetamine, methylenedioxy-methamphetamine (MDMA) and THC, based upon Australian Standard (AS) 4760-2006, ‘Procedures for specimen collection and the detection and quantitation of drugs in oral fluid’. However, the National Association of Testing Authorities (NATA) Australia (established to ensure compliance with international and Australian standards) dismissed the flawed 2006 oral fluid standard for on-site testing. Regardless of NATA raising the alarm at a FACTA Symposium in 2010 and a five-year rule review due in 2011, Standards Australia have done absolutely nothing to fix their faulty standard, still being sold as if in perfect working order by the likes of SAI Global (risk management, standards compliance and information business). A dubious practice from a standard-setting body, a damning demonstration of neglect and failure to deliver ethical and credible standards and a far cry from Standards Australias official Code of Conduct. In July 2013, accreditation of on-site drug testing of oral fluid (AS 4760, Section 3) was suspended by NATA due to significant technical issues with the standard.

drager-drugtest5000-640x640Though the portable drug testing device – the Dräger DrugTest® 5000 – is capable of testing for all sorts of drugs, including cocaine, prescription painkillers and benzodiazepines, current operating procedure is to only test for cannabis, methamphetamine and MDMA. “Someone can be pulled over on a roadside drug test, be literally drugged up to their eyeballs on cocaine and benzo’s, administer the test and be given the all clear to drive”, said New South Wales (NSW) Greens MP, David Shoebridge, in April 2016. “The police will literally wave you through. How is that a rational road safety campaign? These classes of drugs can already be picked up by the existing Dräger 5000 equipment, they just choose not to”, he said. The NSW Minister for Roads, Maritime and Freight claimed the current mobile drug testing cannot detect cocaine. “The technology does not allow for it”, he said in Parliament, in February 2016. He also said police can however require anyone suspected of a cocaine or benzo impairment to undergo a blood and urine test, and they do. “Let me be very clear that these drivers on cocaine or other drugs will not go undetected or unpunished regardless of where they are from”, he said. However, the Dräger Australia & New Zealand website quite clearly states that the system detects a variety of substances such as;

  • Amphetamines
  • Benzodiazepines
  • ∆9-tetrahydrocannabinol (THC)
  • Cocaine
  • Methamphetamines
  • Opiates
  • Methadone
  • Ketamine

Image result for benzodiazepinesDuring the 2013 Australasian Road Safety Research, Policing and Education Conference it was noted that approximately 30% of road deaths are associated with drivers having an illegal blood alcohol concentration (BAC), with evidence over the past decade this proportion has increased. Alcohol contributes to the three major causes of teen death: injury, homicide and suicide. Data from the Coroners Court of Victoria listed the main drugs that contributed to drug-related deaths in 2009–15. Analysis of the data revealed pharmaceuticals contributed to 80% of overdose deaths; benzodiazepines and opioids were the main drug groups involved. Drug overdose deaths rose for a fifth consecutive year in 2016, led by addictive medications such as benzodiazepines, linked to more drug deaths than illegal drugs. In 2015 in Australia, almost twice as many overdose deaths were linked to legal prescription medication, compared to illegal drugs.

The United Kingdom (UK) implemented new drug driving legislation based on a 2013 report by Professor Kim Wolff (Addiction Science, King’s College, London) and a panel of experts, Driving Under the Influence of Drugs, which states;

“Contamination of the buccal (oral) cavity is an issue for the detection of cannabis use since the drug is often used by oral, intra‐nasal or smoking routes of administration (insufflations). ‘Shallow depots’ of cannabis may, following recent use, accumulate in the buccal cavity and produce elevated concentrations in oral fluid for several hours after ingestion. Unfortunately, the cannabinoids do not pass readily from blood into saliva and the detection of … THC in oral fluid is largely reported to be due to contamination of the oral cavity following smoking”.

27F-DRUGS DRIVING TABLE.4

Professor Wolff blogged that they know a great deal about patterns of use concerning cocaine. Its acute effects and “come down” are well described in relation to the deleterious effects on driving behaviour. With regard to drivers consuming benzodiazepines, research has shown that use leads to increased risk of motor vehicle accidents. Specific scientific evidence has been published citing road traffic effects for a raft of different benzodiazepines. The risk of RTA following benzodiazepine use has been demonstrated in several studies in both older and young population groups, estimated to increase the risk of having an accident by 62% compared with non‐use.  Analysis of benzodiazepines by half‐life revealed that those with a long half‐life were associated with an increased risk of RTA; anxiolytics and hypnotics for example, suggesting a greater need for attention to driver‐safety for long acting anxiolytics (temazepam and nitrazepam).

weed-handcuffs

Critics claim Shoebridge and his ilk are making mountains out of molehills, and that anyone who agrees must be living comfortably in the pocket of the “pro-drugs” lobby. But even the most casual, illicit-drug takers have cause to be concerned if they are unable to measure their own ‘body purity’ before getting behind the wheel – the potential for having their lives ruined despite representing no enhanced threat to road safety is very real. The only current option to ensure you’re safe from mobile drug testing is don’t take any illegal drugs or don’t drive, which is not necessarily the most realistic approach to drug safety on the roads. 

r0_56_1080_663_w1200_h678_fmaxShoebridge described NSW state roadside drug testing operations as a highly politicised “zero tolerance extension on the war on drugs dressed up as road safetyIt’s a class war”. Shoebridge maintains cocaine, benzo’s and prescription painkillers are “middle to upper class drugs” which police and politicians are reticent to prosecute on. “There are people driving on our roads with enormously high levels of these drugs in their system and nobody is checking” he said. The Australian Institute of Health and Welfare’s 2013 National Drug Strategy Household Survey reported use of such as cannabis, ecstasy and methamphetamine have been on the decline since 2004 while the proportion of people using cocaine has been increasing since the same year, particularly those aged between 20 to 39 years. “Cocaine use in Australia is currently at the highest levels yet seen”, the report said.

Image result for pharmaceutical benefits schemeAround 80% of all prescription drugs dispensed in Australia are subsidised by the taxpayer funded Pharmaceutical Benefits Scheme (PBS, in existence since 1948). Close to seven million prescriptions for benzodiazepines are dispensed in Australia each year under this scheme and their main indications for use are short-term treatment of anxiety and insomnia. However, such high rates of ongoing benzodiazepine prescribing indicate it is used for long-term problems. This is of concern given evidence of its association with addiction, overdose and other harms such as falls in the elderly and motor vehicle accidents. Benzodiazepines were reported to be the second most commonly misused class of medications, after analgesics, in the 2013 Australian Institute of Health and Welfare, National Drug Strategy Household Survey report. Diazepam, the most commonly prescribed benzodiazepine, is also the most common benzodiazepine found at post-mortem.

“When people are getting false and misleading information from authoritative government sources and rely upon that in their decision making, they fail the test, land up in front of a magistrate, then what more can you do to argue against a genuine mistake of fact?” Shoebridge said. “It’s an enormous problem for police”. There have already been court-cases where these issues were raised, with adjourned cases and judgements NSW police are looking to challenge. The drug testing operation (in NSW) was a $6 million government tender over four years to 2018, just for the devices. On top are costs for drug testing vehicles, police man hours roadside and in court, the magistrate, a police prosecutor and court costs. The cost to tax-payers ranges into even more millions of dollars. “What would be really useful is if NSW police lifted their eyes above their navel and get the international evidence on this growing body of research”, Shoebridge said.

Image result for NSW police lifted their eyes above their navel and get the international evidence on this growing body of research

It’s now generally well-known the devices used by police don’t test for levels that have been proven to cause driver impairment, as breathalysers do for alcohol. Rather, drug testing devices detect tiny trace elements of just three illicit substances, one of which is THC. The Northern Rivers region has been the epicentre of the NSW police blitz on roadside drug testing over the past year (in Queensland, testing has also tripled in both urban and regional areas). Local courthouses, in particular the Lismore Courthouse, have been overwhelmed hearing cases of this type. Michael Balderstone, President of the Nimbin HEMP Embassy has been campaigning for the legalisation of the plant for the last 30 years. Michael is also President of the Australian HEMP Party. He ran as the Western Australian candidate for the party in the 2016 federal election with the aim to “re-legalise and regulate personal, medical and industrial use” of cannabis.

HEMP Party

In an interview in December 2016, Michael was asked about the blitz on roadside drug testing in the Northern Rivers region, what’s happening in the local area and the effect on the community. He replied that it has had a huge effect on the whole of the Northern Rivers community now, for at least a year. “People are regularly getting bust[ed] … it seems that the first test is really unreliable. So there’s no guarantees how efficient it is. And once you’ve registered positive on the first test you’re stuffed … the second test … they send to a lab – 98% … have come back positive. It picks up a tiny trace of pot. You might have smoked a joint two weeks before, or a month before. Or been in a room with your old man smoking. Once you go down on the first test, you’re history”. He went on to say, “We’ve got more car accidents than ever up here. The road tolls up. I can’t say it’s contributed. But it certainly isn’t helping. I know a lot of people who don’t smoke now during the day and they’re much more anxious. They’re worse drivers. If you do smoke, you’re terrified if you see a cop. So I actually think it’s contributed to more anxiety”.

Image result for National Road Safety Strategy australia

The National Road Safety Strategy, established to reduce road deaths and injuries by 30% over ten years, was running around four years behind in some states, the Australian Automobile Association’s last report, released September 2016, stated. The ‘Benchmarking the Performance of the National Road Safety Strategy’ report showed there were 1,273 fatalities on Australian roads in the year to September 2016, an increase from 1,187 a year earlier. It also showed some states are years behind in achieving the targeted lower numbers of road deaths. “The NRSS, signed by all Australian governments, aims to reduce the number of road deaths and serious injuries by at least 30% between 2011 and 2020” AAA Chief Executive Michael Bradley said. “Despite progress in the first few years, we are again seeing increased fatalities on our roads”. Bradley estimated around 626 Australians are seriously injured each week, but without proper national data, it is impossible to know for sure. 

Image result for oral fluid drug concentration measure

An oral fluid drug concentration measure is not causative of any pharmacological effect; it may correlate with some pharmacological effect, but then again it may not. A blood, plasma or serum measure would present a more reasonable case, if calibrated to exclude the lower portions of the dose-response relationship where uncertainty is greatest. Moreover, various reports indicate that even among seasoned ‘recreational’ users, most have insight as to their degree of mental impairment and would judge their ability to drive accordingly. Medical patients reportedly achieve the desired effects to live a normal life and to meet their social obligations.

Public safety is often cited as the reason behind drug driving laws – but many have expressed the view that if that were the case, minimum concentration levels would be prescribed – like the low, mid and high range prescribed concentrations for drink driving charges – rather than charging people for minute quantities which cannot affect driving ability. Such a regime, it is argued, would represent a fairer system – punishing those with very high concentrations – rather than putting everyone on the same boat. But rather than adopt an ‘evidence based’ approach, the NSW Minister for Roads, Maritime and Freight indicated in the first quarter of 2016 that NSW would be targetting all so-called drug drivers;

“The simple message every driver needs to hear from this campaign is that if you take drugs and drive, the boys in blue are going to catch you … We’re throwing millions at enforcement, dedicated drug testing vehicles and campaigns from our Community Road Safety Fund to eradicate and anti-socialise drug driving”.

While it is claimed that illicit drug use is a major factor in road accidents, current legislation does not differentiate between drivers with a level of drugs in their system capable of affecting driving ability, and those who are found with miniscule amounts long after the effects have worn off. It is hoped that the government will ultimately see sense and formulate a fairer approach which prescribes minimum levels, like in the UK and other countries, thereby promoting road safety rather than unfairly sending large numbers of guiltless people to court.

Expanded from Griffith Journal of Law & Human Dignity – The Issue Of Driving While A Relevant Drug, Δ9-Tetrahydrocannabinol, Was Present In Saliva: Evidence About The Evidence, with Drug Policy Implications of Inhaled Cannabis: Driving Skills and Psychoactive Effects, Vaporized Pharmacokinetic Disposition, and Interactions with AlcoholSmoked Cannabis’ Psychomotor and Neurocognitive Effects in Occasional and Frequent SmokersPopulation Pharmacokinetic Model of THC Integrates Oral, Intravenous, and Pulmonary Dosing and Characterizes Short-and Long-Term PharmacokineticsDrug Testing Today – Australian SubStandards, Current Therapeutic Cannabis Controversies and Clinical Trial Design IssuesAustralia is Falling Years Behind on Reducing the Road Death TollAustralian guidelines to reduce health risks from drinking alcoholNational Drug Strategy Household Survey detailed report 2013Legalise It: An interview with Australian Hemp Party President Michael BalderstoneADF Quick Statistics – CocaineADF Quick Statistics – Benzodiazepines, An analysis of single-vehicle fatality crashes in Australia at various Blood Alcohol Concentrations, Prescription drugs led by Valium linked to more deaths than heroin and alcohol, Prescription drug abuse – A timely update, and Magistrate Slams Police for Misadvising About Drug Driving

  1. A drug is designed to produce a specific reaction inside the body as opposed to a medicine, which is a substance designed to prevent or treat diseases. While there is considerable overlap between the two types of substances, these differences are quite important. Most of the medicines that are also drugs are considered “controlled substances”. This means laws govern their use and using them in ways contrary to those laws can lead to criminal charges. Antidepressants are drugs, in that they are designed to help alleviate the physical symptoms of depression. However, they are also used in the treatment of the chemical imbalance that purportedly leads to depression, so also a medicine. Cocaine, on the other hand, is a drug designed to create a specific mental reaction that leads to a “high” for the user. However, the medical establishment does not recognise any medical benefits for cocaine at this time. Over-the-counter anti-inflammatory medicines are designed to treat pain, but they do not have a strong enough effect to fit into a controlled substance classification, unlike stronger pain relievers. This means these are medicines rather than drugs. Understanding the similarities and differences between drugs and medicines is an important part of medical and pharmaceutical training. The very reasons Cannabis is NOT a drug, it is a herb, nor is it a toxin, narcotic nor hallucinogen.
  2. Plasma and serum are cell-free portions of blood. Measured ‘drug’ concentrations within a defined blood specimen may differ quite markedly depending upon the extent of distribution into the blood cells and its affinity for the various proteins dissolved in the cell-free phase. In the case of THC, the blood concentration is nearly one half the corresponding plasma or serum concentration due to minimal uptake of THC into the blood cells. Serum is similar to blood but with clotting-factors removed. This pharmacological minutia affects many quantitative aspects of pharmacology. The various measures are used in particular contexts, unless required for such context, the general term ‘blood’ is used.

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